This grant proposal is in response to specific NIH PAR-03-045 'Nanoscience and Nanotechnology in Biology and Medicine' and utilizes the R21 mechanism. We will extend proof-of-concept nanomechanical cell studies conducted by the Gimzewski & Teitell labs. Using atomic force microscopy (AFM), we have documented novel, treatment- and strain-dependent motion signatures from resting and stimulated yeast cells and have conducted similar but more preliminary measurements in mammalian cells. Importantly, initial experiments indicate that these cell-specific mechanical signals yield real-time diagnostic information about cell structure, metabolism and movement, along with response to chemical and physical stimuli. We specifically seek support to characterize further the nanomechanical features of mammalian cells and to develop a higher-throughput experimental approach. Our new approach will make use of "nano mirrors" fixed to the cell membrane, in place of the AFM tip. These mirrors act as nanoscopic displacement probes and can be interrogated by laser scanning metrology (using an optical lever or a fiber-optic interferometer). This configuration is parallel, enabling simultaneous nanomechanical measurements of hundreds-to- thousands of individual cells. We will document the ability our nano mirror concept to provide information about a cell's state of health and functioning, in a variety of environmental conditions. [unreadable] [unreadable] [unreadable]